Gemcitabine
Identification
- Name
- Gemcitabine
- Accession Number
- DB00441
- Description
Gemcitabine is a nucleoside analog used as chemotherapy. It is marketed as Gemzar® by Eli Lilly and Company. As with fluorouracil and other analogues of pyrimidines, the drug replaces one of the building blocks of nucleic acids, in this case cytidine, during DNA replication. The process arrests tumor growth, as new nucleosides cannot be attached to the "faulty" nucleoside, resulting in apoptosis (cellular "suicide").
Gemcitabine is used in various carcinomas: non-small cell lung cancer, pancreatic cancer, bladder cancer and breast cancer. It is being investigated for use in oesophageal cancer, and is used experimentally in lymphomas and various other tumor types.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Gemcitabine (DB00441)
- Weight
- Average: 263.1981
Monoisotopic: 263.071762265 - Chemical Formula
- C9H11F2N3O4
- Synonyms
- 2'-Deoxy-2',2'-difluorocytidine
- 2',2'-Difluorodeoxycytidine
- 4-amino-1-((2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl)pyrimidin-2(1H)-one
- Gemcitabin
- Gemcitabina
- Gemcitabine
- Gemcitabinum
- External IDs
- LY-188011
- LY188011
Pharmacology
Accelerate your drug discovery research with the industry’s only fully connected ADMET dataset, ideal for:Accelerate your drug discovery research with our fully connected ADMET dataset- Indication
Gemcitabine is indicated for the treatment of advanced ovarian cancer that has relapsed at least 6 months after completion of platinum-based therapy; metastatic ovarian cancer; inoperable, locally advanced (Stage IIIA or IIIB), or metastatic (Stage IV) non-small cell lung cancer; and locally advanced (nonresectable Stage II or Stage III) or metastatic (Stage IV) adenocarcinoma of the pancreas.
- Associated Conditions
- Advanced Ovarian Cancer
- Carcinoma Breast Stage IV
- Locally Advanced Biliary Tract Cancer
- Locally Advanced Non-Small Cell Lung Cancer
- Locally Advanced Pancreatic Adenocarcinoma
- Metastatic Biliary Tract Cancer
- Metastatic Bladder Cancer
- Non-small Cell Lung Cancer (NSCLC), Stage IV
- Advanced Bladder cancer
- Stage 4 Pancreatic adenocarcinoma
- Contraindications & Blackbox Warnings
Contraindications & Blackbox WarningsWith our commercial data, access important information on dangerous risks, contraindications, and adverse effects.Our Blackbox Warnings cover Risks, Contraindications, and Adverse Effects- Pharmacodynamics
Gemcitabine is an antineoplastic anti-metabolite. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the "S" phase (or DNA synthesis phase of the cell cycle), stopping normal development and division. Gemcitabine blocks an enzyme which converts the cytosine nucleotide into the deoxy derivative. In addition, DNA synthesis is further inhibited because Gemcitabine blocks the incorporation of the thymidine nucleotide into the DNA strand. It demonstrates dose-dependent synergistic activity with cisplatin in vitro. In vivo, gemcitabine showed activity in combination with cisplatin against the LX-1 and CALU-6 human lung xenografts, but minimal activity was seen with the NCI-H460 or NCI-H520 xenografts. Gemcitabine was synergistic with cisplatin in the Lewis lung murine xenograft. Sequential exposure to gemcitabine 4 hours before cisplatin produced the greatest interaction.
- Mechanism of action
Gemcitabine inhibits thymidylate synthetase, leading to inhibition of DNA synthesis and cell death. Gemcitabine is a prodrug so activity occurs as a result of intracellular conversion to two active metabolites, gemcitabine diphosphate and gemcitabine triphosphate by deoxycitidine kinase. Gemcitabine diphosphate also inhibits ribonucleotide reductase, the enzyme responsible for catalyzing synthesis of deoxynucleoside triphosphates required for DNA synthesis. Finally, Gemcitabine triphosphate (diflurorodeoxycytidine triphosphate) competes with endogenous deoxynucleoside triphosphates for incorporation into DNA.
Target Actions Organism ADNA cross-linking/alkylationHumans ARibonucleoside-diphosphate reductase large subunit inhibitorHumans UThymidylate synthase inhibitorHumans UUMP-CMP kinase inhibitorHumans - Absorption
The pharmacokinetics of gemcitabine are described by a 2-compartment model.
- Volume of distribution
- 50 L/m^2 [infusions lasting <70 minutes]
- 370 L/m^2 [long infusions]
- Protein binding
Plasma protein binding is negligible (<10%)
- Metabolism
Transformed via nucleoside kinases to two active metabolites, gemcitabine diphosphate and gemcitabine triphosphate. Can also undergo deamination via cytidine deaminase to an inactive uracil metabolite (dFdU).
Hover over products below to view reaction partners
- Route of elimination
Within one (1) week, 92% to 98% of the dose was recovered, almost entirely in the urine. Gemcitabine (<10%) and the inactive uracil metabolite, 2´-deoxy-2´,2´-difluorouridine (dFdU), accounted for 99% of the excreted dose.
- Half-life
Gemcitabine half-life for short infusions ranged from 42 to 94 minutes, and the value for long infusions varied from 245 to 638 minutes, depending on age and gender, reflecting a greatly increased volume of distribution with longer infusions.
- Clearance
- 92.2 L/hr/m2 [Men 29 yrs]
- 75.7 L/hr/m2 [Men 45 yrs]
- 55.1 L/hr/m2 [Men 65 yrs]
- 40.7 L/hr/m2 [Men 79 yrs]
- 69.4 L/hr/m2 [Women 29 yrs]
- 57 L/hr/m2 [Women 45 yrs]
- 41.5 L/hr/m2 [Women 65 yrs]
- 30.7 L/hr/m2 [Women 79 yrs]
- Adverse Effects
Reduce medical errorsand improve treatment outcomes with our comprehensive & structured data on drug adverse effects.Reduce medical errors & improve treatment outcomes with our adverse effects data- Toxicity
Myelosuppression, paresthesias, and severe rash were the principal toxicities, LD50=500 mg/kg (orally in mice and rats)
- Affected organisms
- Humans and other mammals
- Pathways
Pathway Category Gemcitabine Metabolism Pathway Drug metabolism Gemcitabine Action Pathway Drug action - Pharmacogenomic Effects/ADRs
Interacting Gene/Enzyme Allele name Genotype(s) Defining Change(s) Type(s) Description Details Ribonucleoside-diphosphate reductase large subunit --- (A;A) A allele, homozygous / A allele, homozygous ADR Directly Studied Patients with this genotype have increased risk of neutropenia and neurotoxicity with gemcitabine. Details
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Gemcitabine may decrease the excretion rate of Abacavir which could result in a higher serum level. Abatacept The risk or severity of adverse effects can be increased when Gemcitabine is combined with Abatacept. Abciximab The risk or severity of bleeding can be increased when Abciximab is combined with Gemcitabine. Abemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Gemcitabine. Aceclofenac Aceclofenac may decrease the excretion rate of Gemcitabine which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Gemcitabine which could result in a higher serum level. Acenocoumarol The therapeutic efficacy of Acenocoumarol can be increased when used in combination with Gemcitabine. Acetaminophen Acetaminophen may decrease the excretion rate of Gemcitabine which could result in a higher serum level. Acetazolamide Acetazolamide may increase the excretion rate of Gemcitabine which could result in a lower serum level and potentially a reduction in efficacy. Acetylsalicylic acid Acetylsalicylic acid may decrease the excretion rate of Gemcitabine which could result in a higher serum level. 
Improve patient outcomesBuild effective decision support tools with the industry’s most comprehensive drug-drug interaction checker.Learn more - Food Interactions
- No interactions found.
Products
Comprehensive & structured drug product infoFrom application numbers to product codes, connect different identifiers through our commercial datasets.Easily connect various identifiers back to our datasets- Product Ingredients
Ingredient UNII CAS InChI Key Gemcitabine hydrochloride U347PV74IL 122111-03-9 OKKDEIYWILRZIA-OSZBKLCCSA-N - International/Other Brands
- Abine (Dosa) / Abingem (Miracalus) / Acytabin (Intas) / Celgem (Alkem) / Celzar (Celon) / Cytogem (Dr Reddys) / Daplax (Dr Reddys) / Dercin (Egis) / Eriogem (Eriochem) / Fotinex (Fada) / Gebina (Aspen) / Gembio (Bioprofarma) / Gemcired (Dr Reddys) / Gemita (Fresenius) / Gezt (Richmond) / Gitrabin (Actavis) / Gramagen (Lilly) / Jemta (Sandoz) / Nallian (Gedeon Richter) / Oncogem (Grey Inversiones) / Ribozar (Ribosepharm) / Tabin (Crinos) / Xtroz (Ranbaxy)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Act Gemcitabine Powder, for solution Intravenous Actavis Pharma Company Not applicable Not applicable Canada 
Act Gemcitabine Solution Intravenous Actavis Pharma Company 2016-05-02 2019-08-13 Canada Act Gemcitabine Powder, for solution Intravenous Actavis Pharma Company Not applicable Not applicable Canada Gemcitabine Injection, solution 100 mg/1mL Intravenous BluePoint Laboratories 2018-05-25 Not applicable US 
Gemcitabine Injection, solution 100 mg/1mL Intravenous Accord Healthcare Inc. 2018-01-25 Not applicable US Gemcitabine Injection, solution 38 mg/1mL Intravenous Hospira, Inc. 2011-08-22 Not applicable US Gemcitabine Injection, solution 100 mg/1mL Intravenous BluePoint Laboratories 2018-05-25 Not applicable US Gemcitabine Injection, solution 100 mg/1mL Intravenous Accord Healthcare Inc. 2018-08-06 Not applicable US Gemcitabine Injection, solution 38 mg/1mL Intravenous Hospira, Inc. 2011-08-26 Not applicable US Gemcitabine Injection, solution 100 mg/1mL Intravenous BluePoint Laboratories 2018-05-25 Not applicable US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Aj-gemcitabine Powder, for solution Intravenous Agila Jamp Canada Inc Not applicable Not applicable Canada Aj-gemcitabine Powder, for solution Intravenous Agila Jamp Canada Inc Not applicable Not applicable Canada Aj-gemcitabine Powder, for solution Intravenous Agila Jamp Canada Inc Not applicable Not applicable Canada Gemcitabine Injection, powder, lyophilized, for solution 1 g/25mL Intravenous Sagent Pharmaceuticals 2011-07-25 2017-07-31 US Gemcitabine Injection 2 g/52.6mL Intravenous Armas Pharmaceuticals Inc. 2020-01-15 Not applicable US Gemcitabine Injection 38 mg/1mL Intravenous Actavis Pharma, Inc. 2016-04-12 2020-09-30 US Gemcitabine Injection, powder, lyophilized, for solution 200 mg/5mL Intravenous Sun Pharmaceutical Industries, Inc. 2011-07-25 2018-09-30 US Gemcitabine Injection, powder, lyophilized, for solution 1 g/25mL Intravenous Sagent Pharmaceuticals 2014-12-29 Not applicable US Gemcitabine Injection, powder, lyophilized, for solution 1 g/25mL Intravenous Fresenius Kabi USA, LLC 2011-07-26 Not applicable US Gemcitabine Injection, powder, lyophilized, for solution 200 mg/1 Intravenous NorthStar Rx LLC 2018-11-01 Not applicable US
Categories
- ATC Codes
- L01BC05 — Gemcitabine
- Drug Categories
- Anti-Infective Agents
- Antimetabolites
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Carbohydrates
- Cytidine Deaminase Substrates
- Deoxyribonucleosides
- Drugs that are Mainly Renally Excreted
- Enzyme Inhibitors
- Glycosides
- Immunologic Factors
- Immunosuppressive Agents
- Myelosuppressive Agents
- Narrow Therapeutic Index Drugs
- Noxae
- Nucleic Acid Synthesis Inhibitors
- Nucleic Acids, Nucleotides, and Nucleosides
- Nucleoside Metabolic Inhibitor
- Nucleosides
- P-glycoprotein substrates
- P-glycoprotein substrates with a Narrow Therapeutic Index
- Pyrimidine Analogues
- Pyrimidine Nucleosides
- Pyrimidines
- Radiation-Sensitizing Agents
- Ribonucleosides
- Ribonucleotide Reductases, antagonists & inhibitors
- Toxic Actions
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as pyrimidine 2'-deoxyribonucleosides. These are compounds consisting of a pyrimidine linked to a ribose which lacks a hydroxyl group at position 2.
- Kingdom
- Organic compounds
- Super Class
- Nucleosides, nucleotides, and analogues
- Class
- Pyrimidine nucleosides
- Sub Class
- Pyrimidine 2'-deoxyribonucleosides
- Direct Parent
- Pyrimidine 2'-deoxyribonucleosides
- Alternative Parents
- Pyrimidones / Aminopyrimidines and derivatives / Hydropyrimidines / Imidolactams / Tetrahydrofurans / Heteroaromatic compounds / Secondary alcohols / Fluorohydrins / Azacyclic compounds / Oxacyclic compounds show 7 more
- Substituents
- Alcohol / Alkyl fluoride / Alkyl halide / Amine / Aminopyrimidine / Aromatic heteromonocyclic compound / Azacycle / Fluorohydrin / Halohydrin / Heteroaromatic compound show 20 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- organofluorine compound, pyrimidine 2'-deoxyribonucleoside (CHEBI:175901)
Chemical Identifiers
- UNII
- B76N6SBZ8R
- CAS number
- 95058-81-4
- InChI Key
- SDUQYLNIPVEERB-QPPQHZFASA-N
- InChI
- InChI=1S/C9H11F2N3O4/c10-9(11)6(16)4(3-15)18-7(9)14-2-1-5(12)13-8(14)17/h1-2,4,6-7,15-16H,3H2,(H2,12,13,17)/t4-,6-,7-/m1/s1
- IUPAC Name
- 4-amino-1-[(2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2-dihydropyrimidin-2-one
- SMILES
- NC1=NC(=O)N(C=C1)[C@@H]1O[C@H](CO)[C@@H](O)C1(F)F
References
- Synthesis Reference
John A. Weigel, "Process for making gemcitabine hydrochloride." U.S. Patent US6001994, issued May, 1995.
US6001994- General References
- Link [Link]
- External Links
- Human Metabolome Database
- HMDB0014584
- KEGG Drug
- D02368
- KEGG Compound
- C07650
- PubChem Compound
- 60750
- PubChem Substance
- 46506425
- ChemSpider
- 54753
- 12574
- ChEBI
- 175901
- ChEMBL
- CHEMBL888
- ZINC
- ZINC000018279854
- Therapeutic Targets Database
- DAP001246
- PharmGKB
- PA449748
- PDBe Ligand
- GEO
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Gemcitabine
- AHFS Codes
- 10:00.00 — Antineoplastic Agents
- PDB Entries
- 1p62 / 2no0 / 2vpp / 4pd5 / 6nl4
- FDA label
- Download (105 KB)
- MSDS
- Download (69.2 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Active Not Recruiting Other Malignant Neoplasm of Pancreas 1 4 Active Not Recruiting Treatment Adenocarcinoma of the Pancreas 1 4 Active Not Recruiting Treatment Squamous Non-small-cell Lung Cancer 1 4 Completed Treatment Non-Small Cell Lung Carcinoma (NSCLC) 2 4 Not Yet Recruiting Treatment Metastatic Non-Small Cell Lung Cancer 1 4 Recruiting Treatment Pancreatic Ductal Adenocarcinoma 1 4 Recruiting Treatment Peripheral T Cell Lymphoma (PTCL) / Peripheral T-Cell Lymphoma (PTCL) 1 4 Recruiting Treatment Peripheral T-Cell Lymphoma (PTCL) 1 4 Terminated Treatment EGFR Activating Mutation / Metastatic Non-Small Cell Lung Cancer 1 4 Terminated Treatment Malignant Neoplasm of Pancreas 1
Pharmacoeconomics
- Manufacturers
- Teva parenteral medicines inc
- Eli lilly and co
- Packagers
- Eli Lilly & Co.
- Dosage Forms
Form Route Strength Injection, powder, for solution 1000 mg Injection, powder, lyophilized, for solution Intravenous 38 mg/ml Powder, for solution 1000 MG Powder, for solution 200 MG Injection, solution, concentrate Intravenous; Parenteral 40 MG/ML Solution Intravenous 1 g Injection, solution, concentrate Intravenous 10 mg/ml Injection, solution, concentrate Intravenous 100 mg/ml Injection, solution, concentrate Intravenous 40 mg/ml Injection, powder, for solution Parenteral 1 g Injection, powder, for solution Parenteral 200 mg Injection, solution, concentrate Intravenous 38 mg/ml Solution Intravenous 10 mg Solution, concentrate Intravenous 10 mg Solution Intravenous 40 mg Injection, solution, concentrate Intravenous; Parenteral 100 MG/ML Powder, for solution Intravenous 38 MG/ML Powder, for solution Parenteral 38 MG/ML Powder, for solution Parenteral 1 G Powder, for solution Parenteral 2 G Powder, for solution Parenteral 200 MG Powder, for solution 2 G Injection, solution, concentrate Intravenous; Parenteral 38 MG/ML Powder, for solution 1 G Injection, solution Parenteral 10 MG/ML Powder, for solution 2000 MG Injection Intravenous 1 g/26.3mL Injection Intravenous 2 g/52.6mL Injection Intravenous 200 mg/5.26mL Injection Intravenous 38 mg/1mL Injection, powder, for solution Intravenous 200 MG Injection, powder, lyophilized, for solution Intravenous 1 g/1 Injection, powder, lyophilized, for solution Intravenous 200 mg/1 Injection, powder, lyophilized, for solution Intravenous 40 mg/1mL Injection, solution Intravenous 1 g/26.3mL Injection, solution Intravenous 100 mg/1mL Injection, solution Intravenous 2 g/52.6mL Injection, solution Intravenous 200 mg/5.26mL Injection, solution Intravenous 38 mg/1mL Injection Intravenous 10 MG/ML Powder, for solution Intravenous Powder Intravenous Injection, powder, lyophilized, for solution Intravenous 1 g/25mL Injection, powder, lyophilized, for solution Intravenous 200 mg/5mL Solution Intravenous 2 g/52.6ml Injection, powder, lyophilized, for solution Intravenous 2 g/50mL Injection, powder, lyophilized, for solution Intravenous 38 mg/1mL Solution Intravenous Injection Intravenous 1 g Injection Intravenous 200 mg Injection, powder, for solution Intravenous 38 MG/ML Injection Intravenous 1000 mg Injection, solution, concentrate Intravenous 1000 mg/25ml Injection, powder, lyophilized, for solution Intravenous 200 mg Injection Intravenous 2000 mg Injection, solution, concentrate Intravenous 2000 mg/50ml Injection, solution, concentrate Intravenous 200 mg/5ml Powder Intravenous 1000 mg/1vial Powder Intravenous 200 mg/1vial Injection, powder, lyophilized, for solution Intravenous Injection, solution Intravenous 38 mg/ml Injection, powder, lyophilized, for solution Intravenous 1000 mg Injection, powder, lyophilized, for solution Intravenous 1400 mg Injection, powder, lyophilized, for solution Intravenous 2000 mg Injection, powder, for solution 1 g Injection, powder, lyophilized, for solution Intravenous 1140 mg Injection, powder, lyophilized, for solution Intravenous 228 mg Injection, powder, lyophilized, for solution Intravenous 1138.53 mg Injection, powder, lyophilized, for solution Intravenous 227.71 mg Injection, solution, concentrate Parenteral 1000 mg/10ml Injection, solution, concentrate Parenteral 200 mg/2ml Injection, solution, concentrate Parenteral 2000 mg/20ml Injection, powder, for solution Intravenous 1 g Injection, powder, for solution 200 mg Injection, powder, for solution 230 mg Cream 0.1 % Injection Intravenous 1000 mg/100ml Injection Intravenous 200 mg/20ml Injection Intravenous 500 mg/50ml Injection, powder, for solution Injection, solution Intravenous 10 mg/1mL Powder, for solution 38 MG/ML Injection Intravenous 38 MG/ML Injection, powder, lyophilized, for solution Intravenous 1 g Injection, powder, lyophilized, for solution Intravenous 2 g Powder Intravenous 1400 mg/1vial Injection, powder, lyophilized, for solution Intravenous 1000 mg/1vial Injection, powder, lyophilized, for solution Intravenous 200 mg/1vial - Prices
Unit description Cost Unit Gemzar 1 gm Solution Vial 903.93USD vial Gemzar 1 gram vial 869.16USD vial Gemzar 200 mg Solution Vial 180.78USD vial DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5464826 No 1995-11-07 2013-05-07 US US4808614 No 1989-02-28 2010-05-15 US US9241948 No 2016-01-26 2033-07-01 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 168.64 °C Not Available water solubility Soluble Not Available logP -1.4 Not Available pKa 3.6 Not Available - Predicted Properties
Property Value Source Water Solubility 22.3 mg/mL ALOGPS logP 0.14 ALOGPS logP -1.5 ChemAxon logS -1.1 ALOGPS pKa (Strongest Acidic) 11.52 ChemAxon pKa (Strongest Basic) -1.3 ChemAxon Physiological Charge 0 ChemAxon Hydrogen Acceptor Count 6 ChemAxon Hydrogen Donor Count 3 ChemAxon Polar Surface Area 108.38 Å2 ChemAxon Rotatable Bond Count 2 ChemAxon Refractivity 53.25 m3·mol-1 ChemAxon Polarizability 21.45 Å3 ChemAxon Number of Rings 2 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter No ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9814 Blood Brain Barrier + 0.9693 Caco-2 permeable - 0.8957 P-glycoprotein substrate Non-substrate 0.8317 P-glycoprotein inhibitor I Non-inhibitor 0.9557 P-glycoprotein inhibitor II Non-inhibitor 0.9106 Renal organic cation transporter Non-inhibitor 0.939 CYP450 2C9 substrate Non-substrate 0.8634 CYP450 2D6 substrate Non-substrate 0.8484 CYP450 3A4 substrate Non-substrate 0.6016 CYP450 1A2 substrate Non-inhibitor 0.8958 CYP450 2C9 inhibitor Non-inhibitor 0.8633 CYP450 2D6 inhibitor Non-inhibitor 0.8787 CYP450 2C19 inhibitor Non-inhibitor 0.8478 CYP450 3A4 inhibitor Non-inhibitor 0.9032 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8862 Ames test Non AMES toxic 0.6793 Carcinogenicity Non-carcinogens 0.8286 Biodegradation Not ready biodegradable 0.9948 Rat acute toxicity 2.1220 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9948 hERG inhibition (predictor II) Non-inhibitor 0.8314
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Targets
Accelerate your drug discovery research
with our fully connected ADMET & drug target dataset.
Accelerate your drug discovery research with our ADMET & drug target dataset
Yes
Cross-linking/alkylation
References
- Hastak K, Alli E, Ford JM: Synergistic chemosensitivity of triple-negative breast cancer cell lines to poly(ADP-Ribose) polymerase inhibition, gemcitabine, and cisplatin. Cancer Res. 2010 Oct 15;70(20):7970-80. doi: 10.1158/0008-5472.CAN-09-4521. Epub 2010 Aug 26. [PubMed:20798217]
- Ledermann JA, Gabra H, Jayson GC, Spanswick VJ, Rustin GJ, Jitlal M, James LE, Hartley JA: Inhibition of carboplatin-induced DNA interstrand cross-link repair by gemcitabine in patients receiving these drugs for platinum-resistant ovarian cancer. Clin Cancer Res. 2010 Oct 1;16(19):4899-905. doi: 10.1158/1078-0432.CCR-10-0832. Epub 2010 Aug 18. [PubMed:20719935]
- Garcia-Diaz M, Murray MS, Kunkel TA, Chou KM: Interaction between DNA Polymerase lambda and anticancer nucleoside analogs. J Biol Chem. 2010 May 28;285(22):16874-9. doi: 10.1074/jbc.M109.094391. Epub 2010 Mar 26. [PubMed:20348107]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor
- Specific Function
- Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides.
- Gene Name
- RRM1
- Uniprot ID
- P23921
- Uniprot Name
- Ribonucleoside-diphosphate reductase large subunit
- Molecular Weight
- 90069.375 Da
References
- Kwon WS, Rha SY, Choi YH, Lee JO, Park KH, Jung JJ, Kim TS, Jeung HC, Chung HC: Ribonucleotide reductase M1 (RRM1) 2464G>A polymorphism shows an association with gemcitabine chemosensitivity in cancer cell lines. Pharmacogenet Genomics. 2006 Jun;16(6):429-38. [PubMed:16708051]
- Rosell R, Cobo M, Isla D, Camps C, Massuti B: Pharmacogenomics and gemcitabine. Ann Oncol. 2006 May;17 Suppl 5:v13-16. [PubMed:16807441]
- Bepler G, Kusmartseva I, Sharma S, Gautam A, Cantor A, Sharma A, Simon G: RRM1 modulated in vitro and in vivo efficacy of gemcitabine and platinum in non-small-cell lung cancer. J Clin Oncol. 2006 Oct 10;24(29):4731-7. Epub 2006 Sep 11. [PubMed:16966686]
- Smid K, Bergman AM, Eijk PP, Veerman G, van Haperen VW, van den Ijssel P, Ylstra B, Peters GJ: Micro-array analysis of resistance for gemcitabine results in increased expression of ribonucleotide reductase subunits. Nucleosides Nucleotides Nucleic Acids. 2006;25(9-11):1001-7. [PubMed:17065054]
- Nakahira S, Nakamori S, Tsujie M, Takahashi Y, Okami J, Yoshioka S, Yamasaki M, Marubashi S, Takemasa I, Miyamoto A, Takeda Y, Nagano H, Dono K, Umeshita K, Sakon M, Monden M: Involvement of ribonucleotide reductase M1 subunit overexpression in gemcitabine resistance of human pancreatic cancer. Int J Cancer. 2007 Mar 15;120(6):1355-63. [PubMed:17131328]
- Cerqueira NM, Fernandes PA, Ramos MJ: Understanding ribonucleotide reductase inactivation by gemcitabine. Chemistry. 2007;13(30):8507-15. [PubMed:17636467]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Thymidylate synthase activity
- Specific Function
- Contributes to the de novo mitochondrial thymidylate biosynthesis pathway.
- Gene Name
- TYMS
- Uniprot ID
- P04818
- Uniprot Name
- Thymidylate synthase
- Molecular Weight
- 35715.65 Da
References
- Rosell R, Taron M, Sanchez JM, Moran T, Reguart N, Besse B, Isla D, Massuti B, Alberola V, Sanchez JJ: The promise of pharmacogenomics: gemcitabine and pemetrexed. Oncology (Williston Park). 2004 Nov;18(13 Suppl 8):70-6. [PubMed:15655942]
- Huang CL, Yokomise H, Fukushima M, Kinoshita M: Tailor-made chemotherapy for non-small cell lung cancer patients. Future Oncol. 2006 Apr;2(2):289-99. [PubMed:16563096]
- Giovannetti E, Mey V, Nannizzi S, Pasqualetti G, Marini L, Del Tacca M, Danesi R: Cellular and pharmacogenetics foundation of synergistic interaction of pemetrexed and gemcitabine in human non-small-cell lung cancer cells. Mol Pharmacol. 2005 Jul;68(1):110-8. Epub 2005 Mar 28. [PubMed:15795320]
- Zhao XD, Zhang Y: [Routine chemotherapeutic drug treatment effectiveness predictive molecules and chemotherapeutic drug selection]. Ai Zheng. 2006 Dec;25(12):1577-80. [PubMed:17166391]
- Giovannetti E, Mey V, Nannizzi S, Pasqualetti G, Del Tacca M, Danesi R: Pharmacogenetics of anticancer drug sensitivity in pancreatic cancer. Mol Cancer Ther. 2006 Jun;5(6):1387-95. [PubMed:16818496]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
- Marce S, Molina-Arcas M, Villamor N, Casado FJ, Campo E, Pastor-Anglada M, Colomer D: Expression of human equilibrative nucleoside transporter 1 (hENT1) and its correlation with gemcitabine uptake and cytotoxicity in mantle cell lymphoma. Haematologica. 2006 Jul;91(7):895-902. [PubMed:16818276]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Uridylate kinase activity
- Specific Function
- Catalyzes the phosphorylation of pyrimidine nucleoside monophosphates at the expense of ATP. Plays an important role in de novo pyrimidine nucleotide biosynthesis. Has preference for UMP and CMP as...
- Gene Name
- CMPK1
- Uniprot ID
- P30085
- Uniprot Name
- UMP-CMP kinase
- Molecular Weight
- 22222.175 Da
References
- Vernejoul F, Ghenassia L, Souque A, Lulka H, Drocourt D, Cordelier P, Pradayrol L, Pyronnet S, Buscail L, Tiraby G: Gene therapy based on gemcitabine chemosensitization suppresses pancreatic tumor growth. Mol Ther. 2006 Dec;14(6):758-67. Epub 2006 Sep 25. [PubMed:17000136]
- Hsu CH, Liou JY, Dutschman GE, Cheng YC: Phosphorylation of Cytidine, Deoxycytidine, and Their Analog Monophosphates by Human UMP/CMP Kinase Is Differentially Regulated by ATP and Magnesium. Mol Pharmacol. 2005 Mar;67(3):806-14. Epub 2004 Nov 18. [PubMed:15550676]
- Maring JG, Groen HJ, Wachters FM, Uges DR, de Vries EG: Genetic factors influencing pyrimidine-antagonist chemotherapy. Pharmacogenomics J. 2005;5(4):226-43. [PubMed:16041392]
- Lam W, Leung CH, Bussom S, Cheng YC: The impact of hypoxic treatment on the expression of phosphoglycerate kinase and the cytotoxicity of troxacitabine and gemcitabine. Mol Pharmacol. 2007 Sep;72(3):536-44. Epub 2007 Jun 12. [PubMed:17565005]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Zinc ion binding
- Specific Function
- This enzyme scavenges exogenous and endogenous cytidine and 2'-deoxycytidine for UMP synthesis.
- Gene Name
- CDA
- Uniprot ID
- P32320
- Uniprot Name
- Cytidine deaminase
- Molecular Weight
- 16184.545 Da
References
- Giovannetti E, Laan AC, Vasile E, Tibaldi C, Nannizzi S, Ricciardi S, Falcone A, Danesi R, Peters GJ: Correlation between cytidine deaminase genotype and gemcitabine deamination in blood samples. Nucleosides Nucleotides Nucleic Acids. 2008 Jun;27(6):720-5. doi: 10.1080/15257770802145447. [PubMed:18600531]
- Gusella M, Pasini F, Bolzonella C, Meneghetti S, Barile C, Bononi A, Toso S, Menon D, Crepaldi G, Modena Y, Stievano L, Padrini R: Equilibrative nucleoside transporter 1 genotype, cytidine deaminase activity and age predict gemcitabine plasma clearance in patients with solid tumours. Br J Clin Pharmacol. 2011 Mar;71(3):437-44. doi: 10.1111/j.1365-2125.2010.03838.x. [PubMed:21284703]
- Wong A, Soo RA, Yong WP, Innocenti F: Clinical pharmacology and pharmacogenetics of gemcitabine. Drug Metab Rev. 2009;41(2):77-88. doi: 10.1080/03602530902741828. [PubMed:19514966]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Protein homodimerization activity
- Specific Function
- Required for the phosphorylation of the deoxyribonucleosides deoxycytidine (dC), deoxyguanosine (dG) and deoxyadenosine (dA). Has broad substrate specificity, and does not display selectivity based...
- Gene Name
- DCK
- Uniprot ID
- P27707
- Uniprot Name
- Deoxycytidine kinase
- Molecular Weight
- 30518.315 Da
References
- Wong A, Soo RA, Yong WP, Innocenti F: Clinical pharmacology and pharmacogenetics of gemcitabine. Drug Metab Rev. 2009;41(2):77-88. doi: 10.1080/03602530902741828. [PubMed:19514966]
- Marechal R, Mackey JR, Lai R, Demetter P, Peeters M, Polus M, Cass CE, Salmon I, Deviere J, Van Laethem JL: Deoxycitidine kinase is associated with prolonged survival after adjuvant gemcitabine for resected pancreatic adenocarcinoma. Cancer. 2010 Nov 15;116(22):5200-6. doi: 10.1002/cncr.25303. [PubMed:20669326]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
References
- Bergman AM, Pinedo HM, Talianidis I, Veerman G, Loves WJ, van der Wilt CL, Peters GJ: Increased sensitivity to gemcitabine of P-glycoprotein and multidrug resistance-associated protein-overexpressing human cancer cell lines. Br J Cancer. 2003 Jun 16;88(12):1963-70. [PubMed:12799644]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Atpase activity, coupled to transmembrane movement of substances
- Specific Function
- ATP-dependent transporter probably involved in cellular detoxification through lipophilic anion extrusion.
- Gene Name
- ABCC10
- Uniprot ID
- Q5T3U5
- Uniprot Name
- Multidrug resistance-associated protein 7
- Molecular Weight
- 161627.375 Da
References
- Hopper-Borge E, Xu X, Shen T, Shi Z, Chen ZS, Kruh GD: Human multidrug resistance protein 7 (ABCC10) is a resistance factor for nucleoside analogues and epothilone B. Cancer Res. 2009 Jan 1;69(1):178-84. doi: 10.1158/0008-5472.CAN-08-1420. [PubMed:19118001]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Nucleoside transmembrane transporter activity
- Specific Function
- Mediates both influx and efflux of nucleosides across the membrane (equilibrative transporter). It is sensitive (ES) to low concentrations of the inhibitor nitrobenzylmercaptopurine riboside (NBMPR...
- Gene Name
- SLC29A1
- Uniprot ID
- Q99808
- Uniprot Name
- Equilibrative nucleoside transporter 1
- Molecular Weight
- 50218.805 Da
References
- Santini D, Vincenzi B, Fratto ME, Perrone G, Lai R, Catalano V, Cass C, Ruffini PA, Spoto C, Muretto P, Rizzo S, Muda AO, Mackey JR, Russo A, Tonini G, Graziano F: Prognostic role of human equilibrative transporter 1 (hENT1) in patients with resected gastric cancer. J Cell Physiol. 2010 May;223(2):384-8. doi: 10.1002/jcp.22045. [PubMed:20082300]
- Marce S, Molina-Arcas M, Villamor N, Casado FJ, Campo E, Pastor-Anglada M, Colomer D: Expression of human equilibrative nucleoside transporter 1 (hENT1) and its correlation with gemcitabine uptake and cytotoxicity in mantle cell lymphoma. Haematologica. 2006 Jul;91(7):895-902. [PubMed:16818276]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Pyrimidine- and adenine-specific:sodium symporter activity
- Specific Function
- Sodium-dependent and pyrimidine-selective. Exhibits the transport characteristics of the nucleoside transport system cit or N2 subtype (N2/cit) (selective for pyrimidine nucleosides and adenosine)....
- Gene Name
- SLC28A1
- Uniprot ID
- O00337
- Uniprot Name
- Sodium/nucleoside cotransporter 1
- Molecular Weight
- 71583.18 Da
References
- Mackey JR, Yao SY, Smith KM, Karpinski E, Baldwin SA, Cass CE, Young JD: Gemcitabine transport in xenopus oocytes expressing recombinant plasma membrane mammalian nucleoside transporters. J Natl Cancer Inst. 1999 Nov 3;91(21):1876-81. [PubMed:10547395]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Nucleoside transmembrane transporter activity
- Specific Function
- Mediates equilibrative transport of purine, pyrimidine nucleosides and the purine base hypoxanthine. Very less sensitive than SLC29A1 to inhibition by nitrobenzylthioinosine (NBMPR), dipyridamole, ...
- Gene Name
- SLC29A2
- Uniprot ID
- Q14542
- Uniprot Name
- Equilibrative nucleoside transporter 2
- Molecular Weight
- 50112.335 Da
References
- Mackey JR, Yao SY, Smith KM, Karpinski E, Baldwin SA, Cass CE, Young JD: Gemcitabine transport in xenopus oocytes expressing recombinant plasma membrane mammalian nucleoside transporters. J Natl Cancer Inst. 1999 Nov 3;91(21):1876-81. [PubMed:10547395]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Pyrimidine- and adenine-specific:sodium symporter activity
- Specific Function
- Sodium-dependent, pyrimidine- and purine-selective. Involved in the homeostasis of endogenous nucleosides. Exhibits the transport characteristics of the nucleoside transport system cib or N3 subtyp...
- Gene Name
- SLC28A3
- Uniprot ID
- Q9HAS3
- Uniprot Name
- Solute carrier family 28 member 3
- Molecular Weight
- 76929.61 Da
References
- Govindarajan R, Leung GP, Zhou M, Tse CM, Wang J, Unadkat JD: Facilitated mitochondrial import of antiviral and anticancer nucleoside drugs by human equilibrative nucleoside transporter-3. Am J Physiol Gastrointest Liver Physiol. 2009 Apr;296(4):G910-22. doi: 10.1152/ajpgi.90672.2008. Epub 2009 Jan 22. [PubMed:19164483]
Drug created on June 13, 2005 13:24 / Updated on March 04, 2021 11:01